The factors that regulate the formation of myelin and neuroglia during the development of the Central Nervous System (CNS) are poorly understood. Neurobiologists emphasize that neurons are necessary for normal glial development while endocrinologists and cell biologists have demonstrated that myelin and glia fail to develop in the absence of certain hormones. However, the mechanisms by which neurons and hormones exert their effects upon glial development are unknown. Our recent studies of the development of myelin and glia along the optic system (Skoff, '78; Skoff et al., '79) revealed complex developmental patterns that are best explained by a combination of neuronal and local factors. This proposal is designed to investigate neuronal and extrinsic factors in normal development and in a myelin deficient mutant mouse known as Jimpy. A combination of quantitative histologic and autoradiographic (3H-thymidine and 2(14C)-deoxyglucose) studies will be employed to correlate the development of the neuroglial and myelin heterogeneity along the optic system with the vascularization of the nerve and with possible differences in regional metabolism. The effects of hypo- and hyperthyroidism upon myelination and gliogenesis will be quantitatively evaluated using light and electron microscopy. Thymidine autoradiographic studies of Jimpy mice will be continued to determine if the oligodendrocytes and their precursors continue to divide and die without forming myelin. Quantitative ultrastructural studies will also be carried out to determine if the endocrine changes observed in Jimpy-Tabby mice (Skoff et al., '79) are due to the Jimpy gene or to a Tabby marker gene that is linked to the Jimpy gene. Our observations that the female mouse carrying the Jimpy gene exhibits mosaicism provides the basis for continued histologic and biochemical studies of the interaction between genetically different cells in this mutant.